Papel de la disfunción mitocondrial en los cambios estructurales y funcionales de la membrana peritoneal en pacientes tratados con diálisis peritonealefecto de una dieta antioxidante

Abstract

In this work, we have analyzed whether mitochondrial dysfunction in mesothelial cells of the peritoneal membrane, through an increase in the level of oxidative stress and inflammatory mediators, participates in the epithelial-to-mesenchymal transition (EMT) that these cells may undergo in patients treated with peritoneal dialysis (PD). First, ex vivo studies demonstrated that there was a correlation between mitochondrial dysfunction and the EMT status of mesothelial cells, as well as with the time in PD. Furthermore, a positive correlation was evidenced between the free mtDNA in the dialysate, which acts as an indicator of acute mitochondrial damage, and the dialytic function of the peritoneum. Secondly, both the dialysis fluid (DF) and the inflammatory cytokine IL-1ß were described in vitro as having the ability to induce mitochondrial dysfunction in mesothelial cells. This mitochondrial dysfunction increased the expression of the inflammatory mediators COX-2 and IL-8, and the sensitivity of mesothelial cells to inflammatory cytokines. Also, we determined that mitochondrial reactive oxygen species (ROS) and the NF-κB factor were involved in this process. Likewise, mitochondrial ROS were identified as mediators of the EMT process. Finally, it was shown in vitro that natural polyphenol resveratrol protects the mitochondrial function of mesothelial cells, and that it was able to prevent the effects of this dysfunction, positioning it as a potential therapy to preserve the dialytic capacity of the peritoneum during PD treatment. These results could help a better understanding of the pathogenic mechanisms that lead to ultrafiltration failure in PD patients by showing the involvement of the mitochondria in the pathophysiology of the peritoneal membrane.